Arthritis is a chronic multifactorial disease induced when the immune system attacks and begins degrading the body's joints. The disease comes in many forms, including calcific periarthritis, enteropathic arthritis, chronic arthritis, gout, hand arthritis, osteoarthritis, hip and knee osteoarthritis, thumb, Jaccoud's, and juvenile osteoarthritis, oligoarthritis, polyarthritis, and peripheral, psoriatic, rheumatoid, and septic arthritis. Rheumatoid arthritis alone is estimated to affect 1% of the world's population and is twice as prevalent in women as in men.
Reducing inflammation is the most commonly used treatment option in arthritis. The glucocorticosteroids, such as prednisolone and methylprednisolone, are often-used anti-inflammatory drugs. Nonsteroidal anti-inflammatory drugs (NSAIDs) are also used to suppress inflammation. NSAIDs inhibit the cyclooxygenase (COX) enzymes, COX-1 and COX-2, which are central to the production of prostaglandins produced in excess at sites of inflammation. In addition, the inflammation-promoting cytokine, tumor necrosis factor α (TNFα), is associated with multiple inflammatory events, including arthritis, and first generation anti-TNFα therapies are being used clinically.
There is a need however, for the development of therapeutically active drugs that block angiogenesis in the synovial tissue. These drugs should block leucocyte ingress that triggers inflammation.
Several angiogenesis modulating agents, such as TNP470, taxol, thalidomide, and 2-methoxyestradiol, have been tried in rodent models of arthritis with varying success. In the present invention, a substantially cell membrane impermeable compound has been shown to be a very effective treatment of arthritis. Furthermore, there were no signs or symptoms of toxicity associated with the substantially cell membrane impermeable compound.
Therefore, the present invention provides a method of treatment of arthritis using substantially cell membrane impermeable compounds.